Effects of benfluorex on serum triacylglycerols and insulin sensitivity in the corpulent rat

Canadian Journal of Physiology and Pharmacology
J C RussellD N Brindley

Abstract

The JCR:LA-cp rat is obese, insulin resistant, and hyperlipidemic, and the males develop atherosclerosis and ischemic myocardial disease. Benfluorex at 35-40 mg.kg-1 body weight was administered in the food from 10 to 14 weeks of age and resulted in an initial 50% decrease in food consumption. Body weights of male and female rats initially decreased by about 7% and thereafter remained relatively constant, whereas control animals gained about 28% in weight over the treatment period. Pair-fed rats showed body weights virtually identical with those of benfluorex-treated animals. Benfluorex treatment and pair feeding decreased serum triacylglycerol concentrations by about 50%; there was a preferential loss of triacylglycerols containing longer chain fatty acids in the males, whereas this selectivity was not seen in the females. Hyperinsulinemic euglycemic insulin clamp studies were performed using [1-3H]glucose, a tracer that allows for the measurement of total glucose turnover, including hepatic uptake and release. In male cp/cp rats, hyperinsulinemia does not stimulate total glucose turnover, reflecting the very severe insulin resistance, and neither benfluorex treatment nor pair feeding increased total glucose turnover. Hyperins...Continue Reading

References

Jul 22, 1992·Biochemical Pharmacology·C J BaileyC C Thornburn
May 1, 1991·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·J C RussellJ Bar-Tana
Jul 1, 1990·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·J C RussellR M Amy
Sep 1, 1990·Diabetologia·L O Simpson
Jan 1, 1986·Endocrinology·B F MitchellJ R Challis
Aug 1, 1973·Experimental and Molecular Pathology·S Koletsky
May 1, 1972·Endocrinology·L M Zucker, H N Antoniades
May 1, 1994·Metabolism: Clinical and Experimental·J C RussellM Hameed

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Citations

Aug 8, 1998·European Journal of Pharmacology·J C RussellP J Dolphin
Jul 25, 1998·Atherosclerosis·M RichardsonJ C Russell
Nov 25, 2000·Journal of Pharmacological and Toxicological Methods·T A Clark, G N Pierce
Jun 25, 1999·Metabolism: Clinical and Experimental·J C RussellP J Dolphin
Aug 14, 2010·JACC. Cardiovascular Imaging·Kejia CaiPatrick M Winter
Apr 17, 2008·American Journal of Physiology. Endocrinology and Metabolism·James C RussellDavid N Brindley

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